This program explores how serum IgA occasionally permits bacterial bloodstream survival as it modulates the immune response to enteric antigens. Serum IgA is induced by enteric bacteria that are processed through Peyer's patches: it is cleared through the liver. Blockade of complement (c) mediated bacterial clearance by serum IgA plays a role in the pathogenesis of epidemic meningococcal disease and may be involved in that of gonococcal, Haemophilus and streptococcal infections, as well. It is also probable that it contributes to sepsis during severe hepatic cirrhosis. Understanding the function of serum IgA requires a better knowledge of how C is activated on bacterial surfaces. Lysis of neisseria requires recognition of the cell surface by either antibody or c. Properdin (P) is necessary for C-recognition in the absence of specific antibody; P binding augments antibody-initiated lysis through the classical C pathway. Studies planned for the next five years address the molecular mechanism of IgA blockade. They focus on interactions between alternative C pathway components and carbohydrate moieties of immunoglobulins and on bacterial surfaces. the chemical basis of P-recognition will be sought by assessing the ability of native and modified capsular polysaccharides (PS) on inhibit binding of P by zymosan, a highly branched mannose polymer; and by determining the gonococcal cell-surface receptor for P. We will look for a P receptor within PS and oligosaccharides (OS) and on the OS of IgG and IgA. We will use FACS of neisseria tagged with McAb and C components to find out how capsular PS expression influences binding of P and of factors B, H, and I, and what effect PS-specific IgG and IgA have on their binding. We will use mass spectrometry to structure OS that are enzymatically released from myeloma and polyclonal IgA and IgG, and compare the ability of these and other structurally defined and chemically altered OS, to inhibit lysis. We will use monoclonal Abs of different specificities to determine whether IgA blockade is necessarily Ag-specific.